Slide 1: 1 NOVEL DRUG DELIVARY SYSTEM- AN INTRODUCTION : NOVEL DRUG DELIVARY SYSTEM- AN INTRODUCTION Presented By: Miss Devanshi H. Soni
M.pharm- 2nd sem
Guided By: Mr. Haresh Mulani
Department of Pharmaceutics
Dharmaj Degree Pharmacy College, Dharmaj. 2 Slide 3: 3 Why do we need controlled drug delivery? Reasons Medical
- Optimum dose, at the right time, and in the right location Industrial
- Efficient use of expensive ingredients, reduction in production costs Societal
- Beneficial to patients, better therapy, improved comfort and standard of living 3 Basic modes of drug delivery system: : 3 Basic modes of drug delivery system: Targeted Drug Delivery
Controlled Drug Delivery
Modulated Drug Delivery 4 3 Types of Drug Delivery Rates : 3 Types of Drug Delivery Rates Zero order release rate:
k = constant
M = mass of active agent released
t = time 5 dMt/dt = k 2) First Order Release Rate: : 2) First Order Release Rate: After integration, 6 dMt/dt = k(M0- Mt) dMt / dt = KM0e-kt 3) Square root of time release: : 3) Square root of time release: 7 dMt/ dt = K/ t1/2 Slide 8: 8 Factors affect the design of controlled release product : Factors affect the design of controlled release product Physicochemical Properties of drug
Route of Administration
Acute/ chronic therapy
The disease state 9 Slide 10: 10 Controlled Release System Dissolution controlled Diffusion & dissolution controlled Water penetration controlled Chemically controlled Hydrogels Ion-exchange resin Diffusion controlled matrix Reservoir Reservoir & monolithic Encapsulation Matrix cation anion Environment responsive
Diffusion controlled Erodible system
Drug covalently linked with polymer Osmotically controlled
Swelling controlled Classification of controlled release system : Classification of controlled release system 11 1) Matrix Diffusion Types : 1) Matrix Diffusion Types Rigid Matrix Diffusion
Materials used are insoluble plastics such as PVP & fatty acids.
Swellable Matrix Diffusion
Also called as Glassy hydrogels. Popular for sustaining the release of highly water soluble drugs.
Materials used are hydrophilic gums.
Natural: Guar gum, Tragacanth.
Semi-synthetic: HPMC, CMC, Xanthum gum.
Synthetic : Polyacrilamides. 12 Slide 13: 13 Matrix system Rate controlling step:
Diffusion of dissolved drug in matrix. Slide 14: 14 Drug and excipients are mixed with polymers such as Hydroxypropyl methylcellulose (HPMC) and Hydroxypropyl cellulose (HPC).
Tableted by conventional compression.
Release from the tablet takes place by combination of :
water diffuses into the tablet, swells the polymer and dissolves the drug.
drug may diffuse out to be absorbed. Slide 15: 15 MATHEMATICAL EXPRESSION OF MATRIX TYPE OF DRUG DELIVERY SYSTEMS Slide 16: 16 MATHEMATICAL EXPRESSION OF MATRIX TYPE OF DRUG DELIVERY SYSTEMS Q = (A- Cp/2) δp Where A as initial amount of drug solid impregnated in a unit volume of polymer matrix.
Cp = solubility of drug in polymer phase
K = partition coeffient
Ds = diffusivity of drug in solution
Dp = diffusivity of drug in polymer
t = time
dt = differential length of time
δd = thickness of diffusion layer
δp= thickness of outer membrane δp2 + Slide 17: 17 At very early stage of the drug release process, the depletion zone dp is small that,
δp<< The constant drug release rate, = = Slide 18: 18 Now, If the magnitude of dp is substantially large after the lapse
of time or magnitude of partition coefficient
is very large and or the thickness of diffusion layer δd is small, δp2 >> so the drug release rate can be written as, = [(2A-Cp) CpDpt]1/2 Reservoir System : Reservoir System Also called as Laminated matrix device.
Hollow system containing an inner core surrounded in water insoluble membrane.
Polymer can be applied by coating or micro encapsulation.
Rate controlling mechanism - partitioning into membrane with subsequent release into surrounding fluid by diffusion.
Commonly used polymers - HPC, ethyl cellulose & polyvinyl acetate. 19 Slide 20: 20 Reservoir System Rate controlling steps :
Polymeric content in coating, thickness of coating, hardness of microcapsule. MATHEMATICAL EXPRESSION OF RESERVOIR TYPE OF DRUG DELIVERY SYSTEMS : MATHEMATICAL EXPRESSION OF RESERVOIR TYPE OF DRUG DELIVERY SYSTEMS 21 Slide 22: 22 22 MATHEMATICAL EXPRESSION OF RESERVOIR TYPE OF DRUG DELIVERY SYSTEMS
The cumulative amount of drug Q released from unit surface area of reservoir type delivery device is expressed by mathematical expression. This equation suggest that the drug molecules release under the diffusion layer limiting partition controlled process & the drug release rate is linearly proportional to product of solution concentration & solution diffusivity Ds & is inversely proportional to the thickness of hydrodynamic diffusion layer dd. Slide 23: 23 2) Dissolution Matrix Type Also called as Monolith dissolution controlled system since the drug is homogenously dispersed throughout a rate controlling medium waxes (beeswax, carnuba wax, hydrogenated caster oil etc) which control drug dissolution by controlling the rate of dissolution;
1. Altering porosity of tablet.
2. Decreasing its wettebility.
3. Dissolving at slower rate.
Exhibit First order drug release.
Drug release determined by dissolution rate of polymer. Slide 24: 24 Soluble drug Slowly dissolving matrix Slide 25: 25 Encapsulation Called as Coating dissolution controlled system since the drug encapsulated, with slowly dissolving material like cellulose, PEG, PMA (polymethylacrylates) & waxes.
Dissolution rate of coat depends upon stability & thickness of coating. Slide 26: 26 3) Dissolution & Diffusion Controlled Release system Drug encased in a partially soluble membrane.
Pores are created due to dissolution of parts of membrane.
It permits entry of aqueous medium into core & drug dissolution.
Diffusion of dissolved drug out of system.
Ethyl cellulose & PVP mixture dissolves in water & create pores of insoluble ethyl cellulose membrane. Slide 27: 27 4) Osmotic Pressure Controlled System Drug may be osmotically active, or combined with an osmotically active salt (e.g., NaCl).
Semi-permeable membrane usually made from Cellulose acetate.
Drug is pumped out continuously because of osmotic pressure gradient.
More suitable for hydrophilic drug.
Provides zero order release Slide 28: 28 Osmotic Pressure Controlled System Slide 29: 29 5) Chemically Controlled Released Systems Systems that change their chemical structure, when exposed to biological fluids.
Mostly, biodegradable polymers, are designed to degrade as a result of hydrolysis of the polymer chains into biologically safe and progressively smaller moieties and thus releasing API.
It is of two types;
Pendent Chain System Slide 30: 30 Chemically controlled released Systems Erodible Systems
Bulk Erosion: Polymer degradation may occur through bulk hydrolysis.
Surface Erosion: Degradation occur at the surface of the polymers e.g. Polyorthoesters & Polyanhydrides , resulting a release rate is proportional to the surface area of the delivery system. Slide 31: 31 Chemically controlled released Systems Drug delivery from (a) bulk-eroding (b) surface-eroding biodegradable systems Slide 32: 32 Chemically Controlled Released Systems Pendent Chain System
Consist of linear homo or copolymers with drug attached to its backbone chains. e.g. Hydroxy propyl methyacrylamide etc.
Release drug by hydrolysis or enzymatic degradation of the linkages
Follows zero order kinetics, cleavage of the drug is rate determining step. Slide 33: 33 6) Hydrogels Three dimensional structures composed of primarily hydrophilic polymers having chemical or physical cross links which provides a network structure to hydrogels.
Insoluble because of network structure and provides desirable protection of liable drugs, peptides and proteins Slide 34: 34 Hydrogels Drug delivery from matrix swelling-controlled release systems Slide 35: 35 7) Ion-Exchange Resins Controlled ReleaseSystems Such system provide control release of an ionic (ionisable) drug.
Ionisable drug is absorbed on ion-exchange resins granules and then granules are coated with water permeable polymers using spray drying technique.
H+ Cl- in the gastric fluid are exchange with cationic and anionic drugs from the ion-exchange resins. Biodegradable polymers : Biodegradable polymers Polymers: macromolecule consisting of large number of monomers.
Definition: Polymers degraded by biological means such as enzymes, micro-organisms.
The biodegradable polymers can be defined as polymers comprised of monomers linked to one another through functional groups and have a unstable linkage on backbone.
They are biologically degraded or eroded by enzymes introduced in vitro or generated by surrounding living cell or by non- enzymetic process into oligomers or monomers that can be metabolized or excreated. 36 Slide 37: 37 Biodegradable matrices were involved , the drug release would be total from the matrix degradation – controlled device, unless a strong interaction between the drug and degrading matrix. so, it produce more steady release. Characteristics : Characteristics Predictability of biodegradation kinetics
Ease of fabrication / processability
Their toxicity / antigenicity / anti-inflammatory profile following erosion
Absence of toxic endogenous impurities or residual chemicals used in their preparation, e.g. cross-linking agents
Achieve controlled heterogenous erosion without any additive
Ability to withstand sterilization procedures
Degradation products that are excreted readily
Regulatory approval 38 Classification according to the mechanism of polymarization: : Classification according to the mechanism of polymarization: There are two types of polymerization methods reported
These polymerizations are also known as Vinyl polymerization because most of the monomers of interest are compounds that contains a vinyl group .
In general chain polymerization is done by following four types according to the nature of active center
Free radical ,
Anionic chain polymerization ,
Cationic polymerization and
Ziegler- Natta polymerization . 39 Slide 40: 40 40 B. Step growth polymerization:-
It is any two species in the reaction mixture can react by specific reaction between two appropriate functional groups
A polymerization mechanism in which each reaction between monomers is a discrete and independent step. Slide 41: 41 A) NATURAL POLYMERS A) Proteins B) Polysaccharides
1. Albumin 1. Starch
2. collagen 2. Hyaluronic acid
3. Gelatin 3. Dextran
4. Alginic acid
5. Xanthan Gum
6. Guar Gum
11. Cyclodextrin Slide 42: 42 B) Synthetic polymers Polyesters:
eg. PLA, PGA, Poly hydroxy butyrate (PHB),Poly-e- caprolactone(PCL),Polymalic acid,Polydioxanone(PDA)
eg. Poly sebacic acid (PSBA), poly adipic acid (PAPA), Poly terphthalic acid (PTA)
eg. Poly imino carbonate (PIC),
Poly amino acid (PAA) Slide 43: 43 4. Phosphorus Based :
5. Others :
eg. Polycyanoacrylates (PCA),
Polyacetals. Polymer Degradation and Erosion : Polymer Degradation and Erosion Degradation is the process of chain cleavage leading to a reduction in molecular weight. It is occur in 2 phase. 44 Slide 45: 45 PHYSICAL EROSION MECHANISM (A) Bulk-eroding system
Degradation takes place throughout the whole of the polymer matrix.
Loss of physical integrity.
Ingress of water is faster than the rate of degradation
(B) Surface-eroding system
(poly(ortho)esters and polyanhydrides)
Eroded from the surface
Physical integrity maintained
Mass loss is faster than the ingress of water into the bulk Slide 46: 46 Polymer Degradation by Erosion Slide 47: 47 Slide 48: 48 Some Individual applications of Biodegradable polymers Slide 49: 49 Slide 50: 50 Smart polymer Also called ‘Stimulus Responsive’
Similar to biopolymer Smart polymer Undergo reversible changes Hydrophilic state Hydrophobic state Precipitation
Change in size
Alteration in content Driving force for this,
Adding Opposite charge polymer Slide 51: 51 POLYMER THERAPEUTICS It provides for an innovative opportunity to design novel pharmaceuticals that have real potential to improve efficacy in life threatening disease such as cancer.
It offers the opportunity for cell or organ specific targeting. Slide 52: 52 52 Application of SMART POLYMER Immobilized catalyst Drug delivery Chemical valve Thermo-Responsive
surfaces Biometic actuators Bio-Seperation Thermo-Responsive
chromatography Cell detachment Thermally controlled biocatalyst Immobilized viable cells Reversible soluble biocatalyst Aqueous two-phase polymer systems Affinity precipitation References : References www.biodeg.net/Biodegradable polymers
“Controlled Drug Delivery- Concepts and advances” by S.P.Vyas and Roop K.Khar , vallabh prakashan, page no: 1 to 54, 97 to 155. 53 Slide 54: Thank you